rs41283391

Variant names:

• chr17-7017569-C-T
• rs41283391
• ENST00000572453.1:n.2091G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000572453.1(MIR497HG):​n.2091G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 692,550 control chromosomes in the GnomAD database, including 1,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.061 (285 hom., cov: 32)
  • Exomes 𝑓: 0.056 (1030 hom.)
• Consequence: MIR497HG ENST00000572453.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.504
• Publications: 8 publications found

Genes affected

MIR497HG (HGNC:39523): (mir-497-195 cluster host gene)

BACC1 (HGNC:28737): (chromosome 17 open reading frame 49) Enables identical protein binding activity. Predicted to be involved in chromatin organization. Located in cytosol and nucleoplasm. Part of MLL1 complex and NURF complex. [provided by Alliance of Genome Resources, Apr 2022]

RNASEK-C17orf49 (HGNC:44419): (RNASEK-C17orf49 readthrough) This locus represents naturally occurring read-through transcription between the neighboring RNASEK (ribonuclease, RNase K) and C17orf49 (chromosome 17 open reading frame 49) genes. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Jan 2011]

MIR195 (HGNC:31566): (microRNA 195) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BACC1	NM_174893.4	c.*304C>T		downstream_gene_variant		ENST00000439424.6	NP_777553.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C17orf49	ENST00000439424.6	c.*304C>T		downstream_gene_variant		1	NM_174893.4	ENSP00000411851.2
RNASEK-C17orf49	ENST00000547302.3	c.*248C>T		downstream_gene_variant		5		ENSP00000450085.1

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 9264 AN: 152220 Hom.: 285 Cov.: 32

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0331

Gnomad FIN AF: 0.0655

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0635

GnomAD2 exomes AF: 0.0516 AC: 10367 AN: 200770 AF XY: 0.0518

Gnomad AFR exome AF: 0.0670

Gnomad AMR exome AF: 0.0333

Gnomad ASJ exome AF: 0.0397

Gnomad EAS exome AF: 0.000516

Gnomad FIN exome AF: 0.0705

Gnomad NFE exome AF: 0.0671

Gnomad OTH exome AF: 0.0586

GnomAD4 exome AF: 0.0565 AC: 30499 AN: 540212 Hom.: 1030 Cov.: 2 AF XY: 0.0564 AC XY: 16636 AN XY: 294750

African (AFR) AF: 0.0652 AC: 1033 AN: 15844

American (AMR) AF: 0.0345 AC: 1283 AN: 37214

Ashkenazi Jewish (ASJ) AF: 0.0410 AC: 767 AN: 18696

East Asian (EAS) AF: 0.000165 AC: 5 AN: 30288

South Asian (SAS) AF: 0.0357 AC: 2308 AN: 64678

European-Finnish (FIN) AF: 0.0701 AC: 3115 AN: 44446

Middle Eastern (MID) AF: 0.0625 AC: 170 AN: 2720

European-Non Finnish (NFE) AF: 0.0676 AC: 20133 AN: 297974

Other (OTH) AF: 0.0594 AC: 1685 AN: 28352

GnomAD4 genome AF: 0.0608 AC: 9264 AN: 152338 Hom.: 285 Cov.: 32 AF XY: 0.0592 AC XY: 4409 AN XY: 74490

African (AFR) AF: 0.0661 AC: 2749 AN: 41564

American (AMR) AF: 0.0416 AC: 636 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5186

South Asian (SAS) AF: 0.0329 AC: 159 AN: 4828

European-Finnish (FIN) AF: 0.0655 AC: 696 AN: 10626

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0691 AC: 4700 AN: 68036

Other (OTH) AF: 0.0629 AC: 133 AN: 2116

Alfa AF: 0.0620 Hom.: 110

Bravo AF: 0.0611

Asia WGS AF: 0.0220 AC: 77 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.68
PhyloP100		0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41283391; hg19: chr17-6920888;